MiR-200a-3p promotes gastric cancer progression by targeting DLC-1

Li, Zhipeng; Wang, Ying; Liu, Shuai; Li, Weibing; Wang, Zhigang; Jia, Zhangjun; Zhu, Zeyu; Bao, Yuhua

doi:10.1007/s10735-021-10037-7

Cited by 12 publications

(21 citation statements)

References 21 publications

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“…In total, 40 genes showed a significantly decreased expression between hsa-miR-4513 (both alleles combined, purple) and the control samples (grey) [false discovery (FDR) corrected P -value ( Q -value) < 0.01]. ( B ) Expression of hsa-miR-4513 target genes previously identified in the literature ( 8–12 , 16 ), as well as the host gene CSK ( 12 ) in the RNA-Seq data of HUVECs transfected with hsa-miR-4513-A, hsa-miR-4513-G and cel-miR-39 as control. Significant expression differences between the control cel-miR-39 and hsa-miR-4513 samples were only observed for KAT6B ( Q -value < 0.05).…”

Section: Resultsmentioning

confidence: 99%

“…Parallel to the undirected RNA-Seq approach, genes previously linked to hsa-miR-4513 were included in the study. To this end, we conducted a literature search in the context of specific phenotypes, including cardiometabolic phenotypes ( 12 ), age-related macular degeneration ( 16 ) and several types of cancer ( 8–11 ). Further, one study reported that the seed polymorphism rs2168518 in hsa-miR-4513 revealed an effect on expression of CSK , the host gene of hsa-miR-4513 ( 12 ).…”

Section: Resultsmentioning

confidence: 99%

“…Hsa-miR-4513 is an exemplary miRNA harboring a common polymorphism (rs2168518) in its seed region and was recently reported to be overexpressed in several cancer cell lines ( 8–11 ) as well as in cancer tissue ( 11 ). In addition, rs2168518 was associated with several clinically relevant traits and diseases, including cardiovascular phenotypes ( 12–15 ), fasting glucose and lipid traits ( 12 ), age-related macular degeneration ( 15 , 16 ) and different metabolic products in urine ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have suggested target genes of hsa-miR-4513 for selected phenotypes mainly by bioinformatical approaches, and most often without considering the influence of seed polymorphism rs2168518 ( 8–12 , 16 ). Here, we used a global RNA-sequencing (RNA-Seq) approach to determine target genes of hsa-miR-4513, specifically considering the influence of seed polymorphism rs2168518 on target binding.…”

Section: Introductionmentioning

confidence: 99%

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Seed sequence polymorphism rs2168518 and allele-specific target gene regulation of hsa-miR-4513

Kiel

Strunz

Hasler

et al. 2021

Human Molecular Genetics

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MicroRNAs (miRNAs) are small post-transcriptional regulators that offer promising targets for treating complex diseases. To this end, hsa-miR-4513 is an excellent candidate as this gene harbors within its conserved heptametrical seed sequence a frequent polymorphism (rs2168518), which has previously been associated with several complex phenotypes. So far, little is known about the biological mechanism(s) underlying these associations. In an initial step, we now aimed to identify allele-specific target genes of hsa-miR-4513. We performed RNA sequencing in a miRNA overexpression model in human umbilical vein endothelial cells transfected with separated hsa-miR-4513 alleles at rs2168518, namely hsa-miR-4513-G and hsa-miR-4513-A. Genes specifically regulated by the rs2168518 alleles were independently verified by quantitative reverse transcription PCR (qRT-PCR), Western Blot analysis and allele-specific miRNA binding via a luciferase reporter assay. By a text-based search publicly available databases such as Online Mendelian Inheritance in Man and Mouse Genome Informatics were utilized to link target genes of hsa-miR-4513 to previously described phenotypes. Overall, we identified 23 allele-specific hsa-miR-4513 target genes and replicated 19 of those independently via qRT-PCR. Western Blot analysis and luciferase reporter assays conducted for an exemplary subsample further confirmed the allele-specific regulation of these genes by hsa-miR-4513. Remarkably, multiple allele-specific target genes identified are linked via text retrieval to several phenotypes previously reported to be associated with hsa-miR-4513. These genes offer promising candidates for ongoing research on the functional pathobiological impact of hsa-miR-4513 and its seed polymorphism rs2168518. This could give rise to therapeutic applications targeting this miRNA.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Seed sequence polymorphism rs2168518 and allele-specific target gene regulation of hsa-miR-4513

Kiel

Strunz

Hasler

et al. 2021

Human Molecular Genetics

View full text Add to dashboard Cite

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“…For example, an increased level of miR-222 expression suppressed the effect of a breast cancer tumor suppressor, and a decreased miR-222 level increased the expression level of a tumor suppressor ( Said et al, 2021 ). Increased expression of miRNA-200a-3p promotes the growth and development of gastric cancer tumors by suppressing the tumor suppressor ( Li et al, 2021 ). Conversely, miR-345-5p plays the role of a tumor suppressor in lung adenocarcinoma cells, suppressing the oncogene ( Zhou Y. et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Bovine miRNAs with the Potential to Affect Human Gene Expression

et al. 2022

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Milk and other products from large mammals have emerged during human evolution as an important source of nutrition. Recently, it has been recognized that exogenous miRNAs (mRNA inhibited RNA) contained in milk and other tissues of the mammalian body can enter the human body, which in turn have the ability to potentially regulate human metabolism by affecting gene expression. We studied for exogenous miRNAs from Bos taurus that are potentially contain miRNAs from milk and that could act postprandially as regulators of human gene expression. The interaction of 17,508 human genes with 1025 bta-miRNAs, including 245 raw milk miRNAs was studied. The milk bta-miR-151-5p, bta-miR-151-3p, bta-miRNA-320 each have 11 BSs (binding sites), and bta-miRNA-345-5p, bta-miRNA-614, bta-miRNA-1296b and bta-miRNA-149 has 12, 14, 15 and 26 BSs, respectively. The bta-miR-574-5p from cow’s milk had 209 human genes in mRNAs from one to 25 repeating BSs. We found 15 bta-miRNAs that have 100% complementarity to the mRNA of 13 human target genes. Another 12 miRNAs have BSs in the mRNA of 19 human genes with 98% complementarity. The bta-miR-11975, bta-miR-11976, and bta-miR-2885 BSs are located with the overlap of nucleotide sequences in the mRNA of human genes. Nucleotide sequences of BSs of these miRNAs in 5′UTR mRNA of human genes consisted of GCC repeats with a total length of 18 nucleotides (nt) in 18 genes, 21 nt in 11 genes, 24 nt in 14 genes, and 27–48 nt in nine genes. Nucleotide sequences of BSs of bta-miR-11975, bta-miR-11976, and bta-miR-2885 in CDS mRNA of human genes consisted of GCC repeats with a total length of 18 nt in 33 genes, 21 nt in 13 genes, 24 nt in nine genes, and 27–36 nt in 11 genes. These BSs encoded polyA or polyP peptides. In only one case, the polyR (SLC24A3 gene) was encoded. The possibility of regulating the expression of human genes by exogenous bovine miRNAs is discussed.

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Circulating microRNA profiling for prediction of oncological outcomes in prostate cancer patients following radical prostatectomy

et al. 2022

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Background: Although radical prostatectomy is associated with good long-term oncological outcomes, approximately 30% of patients present biochemical recurrence, whereupon salvage treatments are required. Identification of novel molecular biomarkers to predict cancer behavior is clinically important. Here, we developed a novel microRNA (miRNA)-based prognostic model for patients who underwent radical prostatectomy. Methods: We retrospectively investigated the clinical records of 295 patients who underwent radical prostatectomy between 2009 and 2017. We randomly assigned these cases into training or validation sets. The prognostic model was constructed using Fisher linear discriminant analysis in the training set, and we evaluated its performance in the validation set.Results: Overall, 72 patients had biochemical recurrence. A prediction model was constructed using a combination of three miRNAs (miR-3147, miR-4513, and miR-4728-5p) and two pathological factors (pathological T stage and Gleason score). In the validation set, the predictive performance of the model was confirmed to be accurate (area under the receiver operating characteristic curve: 0.80; sensitivity: 0.78; specificity: 0.76). Additionally, Kaplan-Meier analysis revealed that the patients with a low prediction index had significantly longer recurrence-free survival than those with a high index (p < 0.001).Conclusions: Circulating miRNA profiles can provide information to predict recurrence after prostatectomy. Our model may be helpful for physicians to decide follow-up strategies for patients.

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MiR-200a-3p promotes gastric cancer progression by targeting DLC-1

Cited by 12 publications

References 21 publications

Seed sequence polymorphism rs2168518 and allele-specific target gene regulation of hsa-miR-4513

Seed sequence polymorphism rs2168518 and allele-specific target gene regulation of hsa-miR-4513

Identification of Bovine miRNAs with the Potential to Affect Human Gene Expression

Circulating microRNA profiling for prediction of oncological outcomes in prostate cancer patients following radical prostatectomy

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